Prolonged brain cytokine elevation and microgliosis following exposure to World Trade Center dust particulate matter in male spontaneously hypertensive rats.

Exposure to World Trade Center (WTC) dust following the September 11, 2001 attacks has been linked to numerous negative health outcomes in First Responders, including cognitive impairment disproportionately impacting First Responders with aging. However, the mechanisms underlying neurocognitive decline remain poorly characterized. This investigation examined the effects of WTC dust exposure on myelin integrity and neuroinflammatory signaling in twelve-week old male spontaneously hypertensive rats. To model Ground Zero exposure in First Responders, WTC dust was intratracheally administered for two consecutive days (2.43 [± 0.78] mg/day).  It was hypothesized that WTC dust exposure would enhance neuroinflammatory signaling and promote an earlier, progressive decline of myelin abundance. Rats were euthanized at 3 and 12 mo post-exposure. Changes in myelin abundance (Black-Gold II), myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), and microglial responses (ionized calcium-binding protein; Iba1) were assessed through immunohistochemical staining, and cytokines were measured in brain homogenates. WTC dust exposure resulted in increased Black-Gold II staining at 3 mo despite no changes in MBP or CNPase. In contrast, microglial activation and IL-1β concentrations were elevated in dust-exposed rats at 12 mo. Collectively, these data suggest WTC dust exposure induces sustained neuroinflammatory signaling and may elicit a compensatory myelin response indicative of early neurodegeneration.